• Confirmed anhydramnios before 22 weeks GA for patients with FRF or confirmed diagnosis of CoBRA.
  • Anhydramnios in the absence of ruptured membranes (ROM) on ultrasound.
  • No significant bladder filling on ultrasound.
• Consent is signed and first therapeutic amnioinfusion can and does occur before 26 weeks and 0 days gestational age.
• Confirmation that the expectant mother does not wish to undergo termination of the pregnancy.
• Age ≥ 18 years of age for expectant mothers.
• Willingness to be followed and deliver at a RAFT center.
• Willingness for postnatal care to be performed at a RAFT center until discharge.
• Completed consults with Pediatric Nephrology, Neonatology, Transplant Surgery, Pediatric surgery, Maternal-Fetal Medicine Specialist, and Licensed Clinical Social Worker and a Genetic Counselor.

• Cervix less than 2.5 cm in length.
• No significant pathogenic or likely significant pathogenic findings on Karyotype or Microarray.
• Other significant congenital anomalies in the fetus.
• Evidence of chorioamnionitis or abruptio placentae.
• Evidence of rupture of membranes or chorioamniotic separation.
• Evidence of preterm labor.
• Multiple gestation.
• Severe maternal medical condition in pregnancy.
• Maternal depression as assessed by a Beck Depression Inventory score equal to or greater than 17 that is refractory to treatment.
• Technical limitations precluding amnioinfusion.

• Women of reproductive age, 18 – 49 years.
• Seen for clinical care by an obstetrician/gynecologist or cardiologist; advanced practice nurse or physician assistant working in the selected practice.

• Complex congenital heart disease (single ventricle physiology, complex cardiac surgery or significant shunts with cardiac structural changes).
• Significant conduction abnormalities.

• Female age 18 or older at the time of signing informed consent.
• Ultrasound confirmation of singleton pregnancy.
• GA ≥ 9 weeks at the time of first sample collection.
• Willing and able to provide written informed consent.
• Willing and able to comply with study procedures, including blood sample and neonatal buccal swab.
• Cohort 1: Ultrasound confirmation of VT Pregnancies:
  • Ultrasound confirmation of VT;
  • Spontaneous fetal demise of one twin or empty sac.
• Cohort 2: High Risk for VT Pregnancies:
  • Panorama yielding “high risk for twin/VT/triploidy” result;
  • Ultrasound confirmation of single gestation;
  • No evidence of triploidy.

• Known monozygotic twin pregnancy.
• Multiple gestation.
• VT pregnancy resulting from iatrogenic fetal demise.
• GA < 9 weeks.
• Evidence of triploidy other than Panorama test results.
• Any confounding complication or condition that, in the opinion of the investigators, precludes participation in the study; this may include a cancer diagnosis, organ transplant, pregnancy utilizing an egg donor, or other findings that may interfere with interpretation of Panorama results.

Eligibility last updated 10/19/21. Questions regarding updates should be directed to the study team contact.

• Subject scheduled for vaginal birth.
• Subject gestating a single fetus.
• Subject nulliparous, or had a previous pregnancy terminated within 24 weeks gestation.
• Subject able and willing to comply with the protocol required follow-up visits.
• Subjects able and willing to provide written informed consent prior to enrollment.
• In the opinion of the investigator, the subject has sufficient mental capacity to understand the informed consent form (ICF), comply with the protocol requirements, and provide clinically relevant and reliable feedback regarding their experience with the device.
• Subject receives epidural anesthesia during labor prior to using the device.
• Subject 18 years of age or older at time of consent.

• Subject has high likelihood of less than 1 hour of potential device dilation time after she arrives at the hospital.
• Subject has need for or is planning a Caesarean-section.
• Subject begins labor with less than 36 weeks gestation.
• Subject has neurological diseases; e.g., Multiple Sclerosis, that may result in unrelated pelvic disorders, or has been diagnosed with HIV.
• Subject has muscular or skin disorder that affects elasticity of tissue, such as scleroderma or lupus.
• Subject has evidence of local or systemic infection, or has active herpes infection.
• Subject has any prior surgical procedures to the vaginal anatomy which could lead to pelvic dysfunction, pelvic fractures, or pelvic soft tissue injuries.
• Subject has any general health condition or systemic disease that may represent, in the opinion of the investigator, a potential increased risk associated with device use or pregnancy.
• Subject has placenta previa or vasa previa.
• Known significant chromosomal or structural fetal anomalies.
• Category 2 and/or 3 fetal tracing that is unresolved.

Eligibility last updated 9/2/21. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria
•Healthy Volunteers:

• Male and female volunteers aged 18-80 years old.
• No significant medical conditions or gastrointestinal symptoms by interview or questionnaire:
  • Having capacity to provide written informed consent before participating in the study;
  • Able to communicate adequately with the investigator and to comply with the requirements for the entire study.

Inclusion Criteria
•Patients:

• Male and female volunteers aged 18-80 years.
• Persistent upper gastrointestinal symptoms (nausea, vomting, bloating, post prandial fullness or post prandial pain) for > 6 months.
• Having capacity to provide written informed consent before participating in the study.
• Able to communicate adequately with the investigator and to comply with the requirements for the entire study.

Exclusion Criteria
•Healthy Volunteers and Symptomatic Patients: 

• Severe nausea or vomiting, which may preclude study assessments.
• Use of medications that, in the opinion of the investigator have the potential, to alter GI motility (e.g., narcotics, medications with significant anticholinergic effects, prokinetic agents) and which cannot be discontinued for 4 half-lives prior to the imaging studies.
• Clinical evidence of significant cardiovascular, respiratory, renal, hepatic, gastrointestinal, hematological, neurological, psychiatric or other disease that may interfere with the objectives of the study.  A history of inflammatory bowel disease (e.g, Crohn’s disease or ulcerative colitis).  However, participants with microscopic or collagenous colitis will be eligible to participate.
• Prior gastric or major intestinal (i.e., resection of > 50 cm) or colonic surgery (i.e., hemi or subtotal colectomy).  Appendectomy, cholecystectomy, tubal ligation, hysterectomy, herniorrhaphy, and limited colonic resection are permissible.
• Participants who are allergic to eggs or decline to consume milk.
• History of radiation therapy to the abdomen.
• Pregnant women, breast-feeding women, prisoners and institutionalized individuals.
• Treatment with GLP-1 agonists and amlyin which cause vagal blockade and may affect central processing of pain.
• Positive tissue transglutaminase antibodies (TTG).
• Poor peripheral venous access, if central venous access is not available.
• Any other condition or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for the study.

Eligibility last updated 7/18/22. Questions regarding updates should be directed to the study team contact.

• Patients with pouch-related conditions.
• Chronic antibiotic refractory pouchitis (CARP).
• Crohn’s disease (CD) of the pouch.

• None.

• ASA classification I to III, older than or equal to 18 years old.
• All genders.
• Presenting for primary total knee replacement for degenerative joint disease.
• Patient capable of providing their own informed consent.

• Vulnerable study populations including prisoners.
• Patients with a contralateral total knee arthroplasty < 2 years prior to the index procedure.
• Compromised health barring them from proceeding with surgery including acute or chronic kidney injury identified pre-operative.
• Patients unable to provide their own informed consent.
• Pregnancy.
• Patients with documented chronic pain syndromes.
• Patients with a history of prolonged daily opioids (more than 1 month) with an oral morphine equivalent of greater than 5mg/day.
• BMI > 45 kg/m^2.
• Allergies to any component of the study medications, including specific history of type 1 hypersensitivities to any NSAID.
• Patients with impaired cognitive function.
• Major systemic illnesses such as severe renal (estimated glomerular filtration rate less than 50ml/min), coronary artery disease requiring a bypass graft (CABG), other cardiac problems including congestive heart failure (CHF New York Heart Association class III to IV), or severe hepatic disorders defined as current or past diagnosis of acute/subacute liver necrosis, acute hepatic failure, chronic liver disease, liver abscess, hepatic coma, hepatorenal syndrome and other disorders of the liver.

Eligibility last updated 10/12/21. Questions regarding updates should be directed to the study team contact.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 2/15/23. Questions regarding updates should be directed to the study team contact.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 4/21/23. Questions regarding updates should be directed to the study team contact.

• Vulnerable patients as defined by one or more of the following criteria:
  • Age 65 years or older;
  • Having HCT-CI scores of ≥ 3 (for patients that could be 20 years old and older);
  • Having frailty as determined by walk speed of < 0.8 m/s using 4-meter walk test (for patients that could be 40 years old and older).
• Patients considered or referred for allogeneic HCT to treat a hematological malignant or non-malignant disease.
• Able to speak and read English – interaction with the interventionist trainer and endpoint measurement must occur in English.
• Willing and able to provide informed consent.
• Stated willingness to comply with study procedures and reporting requirements.
• Planned allogeneic HCT within 3 weeks – all types of donors and all sorts of conditioning regimens are allowed. Patients with suspected active disease (relatively old disease staging or relatively old intervention) or significant comorbidity (e.g., suspicious untreated pulmonary nodules) based on prior evaluations, that could delay the transplant would be considered for enrollment within a tighter window (10-14 days before allogeneic HCT) to allow for completed pre-HCT work-up evaluations that would confirm readiness to proceed with transplant.
• Able to exercise at low to moderate intensity.
• Adequate cardiopulmonary reserve, as judged by data from the patient’s electronic medical record as to whether a patient could walk up one flight of stairs, no need for supplemental oxygen, and/or physician judgment.

• Orthopedic, neurologic or other problems which prevent safe ambulation and protocol adherence. Information on prior falls and other recent orthopedic or neurologic problems will be used to make judgment about protocol eligibility.
• Participation in another intervention clinical trial with HRQOL as a primary endpoint.
• Planned donor lymphocyte infusion (DLI) within 90 days post-transplant.
• Planned anti-cytotoxic therapies, other than tyrosine kinase inhibitors or single-agent monoclonal antibody, or FLT-3 inhibitors within 90 days of post-transplant unless pre-approved by the protocol Principal Investigator (PI).

• Patients with either an imaging diagnosis of HCC by CT or MRI (LI-RADS 5) confirmed by a board-certified abdominal radiologist, or with biopsy-proven HCC.
• Already enrolled in ongoing Transform the Practice or Department of Defense 68Ga-PSMA studies.
• PSMA avid HCC detected by 68Ga-PSMA PET/CT after intravenous administration of 68Ga-PSMA confirmed by a board certified nuclear radiologist.
• Undergoing planned hepatic artery embolization (HAE) per standard clinical care.
• Male or female with age greater than 18 years, with the capacity and willingness to provide a written informed consent.

• Subjects requiring emergent surgery for a ruptured/bleeding HCC.
• Pregnant and/or breast-feeding subjects. A negative pregnancy test within 48 hours of the PET scan.
• Subjects with higher than the weight/size limitations of PET/CT scanner.

Eligibility last updated 10/8/21. Questions regarding updates should be directed to the study team contact.

• Males and females 21 years of age or older.
• Receiving care in an intensive care unit.
• Expected to remain in the ICU for at least 48 hours after enrollment.
• Use of indwelling urinary catheter as standard care at the time of enrollment.
• Subject must have acute kidney injury (KDIGO Stage 2 or Stage 3) at the time of sample collection.
• Urine sample must be collected within 36 hours of meeting KDIGO Stage 2 criteria.
• Written informed consent provided by patient or legally authorized representative (LAR).

• Individuals under 21 years of age.
• Prior kidney transplantation.
• Comfort-measures-only status.
• Already receiving dialysis (either acute or chronic) or in imminent need of dialysis at the time of enrollment.
• Known infection with human immunodeficiency virus (HIV) or active hepatitis (acute or chronic).
  • NOTE: HIV or hepatitis testing need not be performed for enrollment in this study. 
• Special populations, pregnant women, prisoners or institutionalized individuals.

• Age 18 and older at time of enrollment.
• Confirmed diagnosis of CLL/SLL requiring therapy per iwCLL 2018 criteria.
• Previous treatment with at least one line of therapy that may include a covalent Bruton's tyrosine kinase (BTK) inhibitor.
• Platelets ≥ 50 x 10⁹/liter (L), hemoglobin ≥ 8 grams/deciliter (g/dL) and absolute neutrophil count ≥ 1.0 x 10⁹/L.
• Adequate organ function.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.
• Estimated creatinine clearance ≥ 30 milliliters per minute (mL/min).
• Willingness of men and WOCBP, and their partners, to both observe barrier and highly effective birth control methods as outlined in Section 10.2 and below for the duration of treatment and for 1 months following the last dose of study treatment or 12 months after the last dose of rituximab, whichever is later. WOCBP are defined as those women following menarche and who are not postmenopausal (or 2 years of nontherapy-induced amenorrhea or surgically sterile). WOCBP must utilize 2 effective forms of contraception with at least 1 form of highly effective contraception methods as outlined below. In addition, male partners must use a barrier method (condoms) for the duration of treatment and for 1 months following the last dose of study treatment or 12 months after the last dose of rituximab, whichever is later. Male patients with partners who are WOCBP must use a barrier method (condoms) and their partner must also use a highly effective form of contraception as listed below for the duration of treatment and for 1 month following the last dose of study treatment or 12 months after the last dose of rituximab, whichever is later.
• Highly effective birth control methods with a failure rate of less than 1% per year when used consistently and correctly are recommended (CTFG 2020): a. Combined estrogen and progestin containing hormonal contraception associated with inhibition of ovulation given orally, intravaginally, or transdermally b. Progestin-only hormonal contraception associated with inhibition of ovulation given orally, by injection, or by implant c. Intrauterine device (IUD) d. Intrauterine hormone-releasing system (IUS) e. Bilateral tubal occlusion f. Vasectomized partner g. Sexual abstinence: Considered a highly effective method only if defined as refraining from heterosexual intercourse during an entire period of risk associated with the study treatment. The reliability of sexual abstinence will be evaluated in relation to the duration of the study and to the usual lifestyle of the patient.
• Women with a history of breast cancer may not use hormone containing contraception (a, b, or d). One of the other listed methods above should be selected.
• Women of childbearing potential using hormonal contraception methods should also use a barrier method as a second form of contraception.
• Sperm and oocyte donation are prohibited during the duration of participation on this protocol and for 1 months after the last dose of study treatment, or at least 12 months following last dose of rituximab, whichever is later.
• Willing and capable of giving signed informed consent as described in Section 10.1.2, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.

• Known or suspected Richter's transformation at any time preceding enrollment.
• Prior therapy with a non-covalent (reversible) BTK inhibitor.
• Patients requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist.
• Current treatment with strong cytochrome P450 (CYP) 3A4 (CYP3A4) inhibitors or inducers and/or strong P-glycoprotein (P-gp) inhibitors.
• Prior therapy with venetoclax.
• Central nervous system (CNS) involvement.
• Active uncontrolled systemic bacterial, viral, fungal, or parasitic infection.
• Known human immunodeficiency virus (HIV) infection, regardless of cluster of differentiation 4 (CD4) count.
• Allogeneic stem cell transplantation (SCT) or chimeric antigen receptor (CAR)-T within 60 days.
• Active hepatitis B or hepatitis C.
• Known active cytomegalovirus (CMV) infection.
• Uncontrolled immune thrombocytopenic purpura (ITP) or autoimmune hemolytic anemia (AIHA).
• Significant cardiovascular disease.
• Vaccination with a live vaccine within 28 days prior to randomization.
• Patients with the following hypersensitivity:
  • Known hypersensitivity to any component or excipient of pirtobrutinib and venetoclax;
  • Prior significant hypersensitivity to rituximab;
  • Known allergy to allopurinol and inability to take uric acid lowering agent.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 12/21/23. Questions regarding updates should be directed to the study team contact.

• Subjects who are ≥ 18 years of age.
• Subjects who are known to be positive for syphilis antibodies using routine, standard of care serologic assays.

• Subjects who are < 18 years of age.
• Subjects who are unable to give informed consent.

Eligibility last updated 11/19/21. Questions regarding updates should be directed to the study team contact.

Subjects will be eligible for the study if they meet all of the following criteria at the Baseline Screening:

• Able and willing to give informed consent by voluntarily providing written informed consent in accordance with governing Institutional Review Board.
• 18 to 70 years of age, inclusive at the time of screening.
• History indicative of meniscal pathology (e.g., pain, mechanical symptoms described as locking, clicking or giving way).
• Physical exam consistent with meniscus tear (e.g., locked joint, joint line tenderness and/or pain on meniscal compression).
• If prior ligament reconstruction, the study knee is clinically stable.
• Meniscal repair to be performed arthroscopically.
• Preoperative MRI evidence consistent with a horizontal cleavage or complex meniscus tear in the symptomatic compartment.
• Willing and able to comply with all study procedures and visit requirements, including MRIs, X-rays, and Case Report Forms (CRFs) completed by the subject.

Consented subjects may be included in the study only if, upon arthroscopic inspection during the procedure, their meniscal study lesion meets all of the following criteria:

• Meniscal tear amenable to repair with NOVOSTITCH PRO with or without the use of adjunct devices per the exclusion criteria.
• Tear pattern is one of the following:
  • Horizontal cleavage tear (HCT); or
  • Complex multi-planar tear (combination of at least two of the following tears: horizontal, oblique, radial, vertical).

Subjects will be excluded from the study if they meet any of following criteria at the Baseline Screening:

• Arthritis in the study knee (Kellgren-Lawrence Grade 3 or higher).
• Body Mass Index (BMI) ≥ 40 kg/m^2.
• Previous surgical meniscal repair or meniscectomy of the study meniscus.
• Unstable knee.
• Clinically significant malalignment of the study knee, and/or requiring osteotomy, and/or correction.
• History of constitutional/systemic inflammatory/arthritic problem or pain condition, history of knee infection, vascular condition of legs, benign neoplasms of knee, hepatitis, and/or HIV.
• Currently on any immunosuppressive therapy.
• Expected to undergo any other surgical treatment of either knee.
• Previously enrolled in the study (no bilateral knee surgeries).
• Surgical procedures other than those listed in the Indications for Use.
• Patient conditions including insufficient quantity or quality of tissue.
• Insufficient blood supply or previous infections which may hinder the healing process.
• Foreign body sensitivity. If material sensitivity is suspected, testing should be completed prior to suture implantation.
• Conditions which may limit the patient's ability or willingness to follow postoperative care instructions.
• Any concomitant painful or disabling disease, condition or post-procedure status of either lower extremity that would interfere with evaluation or rehabilitation of the study knee.
• Pregnant or planning to become pregnant in the next 2 years.
• Subject does not understand a language in which the PROs and EQ-5D-5L are available.

Subjects will be excluded from the study if their study meniscus lesion meets any of the following criteria at arthroscopy:

• Ramp tears.
• Root or other tear type requiring tibial fixation.
• Tears requiring repair of both meniscus in the study knee.
• Intact or partially intact meniscus tear that, in the opinion of the Investigator, does not require repair.
• Poor meniscal tissue quality such that it will not hold a suture.
• For HCTs:
  • Use of any capsular fixation device; or
  • Any portion of the meniscal tear is repaired using a device to place stitches other than NOVOSTITCH PRO, Meniscus Mender II, or Meniscal Stitcher or FIRSTPASS MINI marketed by Smith + Nephew Inc.
• For complex tears:
  • Any portion of the meniscal tear is repaired using a device to place stitches other than NOVOSTITCH PRO, Meniscus Mender II, Meniscal Stitcher, FIRSTPASS MINI, FAST-FIX 360; or
  • ULTRA FAST-FIX marketed by Smith + Nephew Inc.
• Clinically significant (zone 1 and/or zone 2) tear in the contralateral compartment to the study meniscus.
• Performance of a significant concomitant procedure (e.g., ACL reconstruction or repair, cartilage repair or restoration) intended as a therapeutic intervention on the study knee.
• Presence of infection.
• Articular cartilage damage in the study knee, defined as Modified Outerbridge Grade III or higher.

• Age:  ≥ 18 years.
• Male with original diagnosis of adenocarcinoma of the prostate with prior definitive therapy.
• Suspicion of recurrence or persistence.
• After radiotherapy or cryotherapy: 3 consecutive PSA rises and/or PSA rise by 2.0 ng/mL or more above nadir (ASTRO-Phoenix).
• After prostatectomy, PSA > 0.2 ng/mL on 2 or more determinations (recurrence), or failure of PSA to fall to undetectable levels post-prostatectomy (persistence) (American Urological Association).
• For patients who previously had radical prostatectomy, salvage radiotherapy is one likely treatment plan; for patients who initially underwent radiotherapy (including brachytherapy), confirmation of low volume disease is needed to define (local) treatment.
• Life expectancy of 6 months or more as judged by the investigator.
• Willing and able to undergo all study procedures.
• Informed consent in writing.

• Age: less than 18 years.
• Contraindications to any of the ingredients of [18F]PSMA-1007.
• Close affiliation with the investigational site.
• At the time of enrolment into this study, participating in another therapeutic clinical trial or has completed study participation in another therapeutic clinical trial within 5 days of enrolment into this trial.
• Having been previously enrolled in this clinical trial.
• Mental conditions rendering the subject incapable to understand the nature, scope, and consequences of the trial -Being clinically unstable or requiring emergency treatment.
• Patients who are unwilling to consider a biopsy if clinically recommended.
• Patients who are unable to undergo a PET/CT scan.
• Patients for whom systemic therapy is the most likely course regardless of PET findings.

Eligibility last updated 8/27/21. Questions regarding updates should be directed to the study team contact.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 10/13/22. Questions regarding updates should be directed to the study team contact.

• Males or females, aged ≥ 50 years and ≤ 89 years.
• An ETDRS BCVA letter score between ≤ 78 and ≥ 40 in the study eye at Screening Visit 1.
• If both eyes are eligible, the study eye must be the participant’s worse-seeing eye, as determined by the investigator prior to randomization.
• Must have a diagnosis of subfoveal CNV secondary to AMD in the study eye, along with fluid within the parafovea (3-mm center of the macula, based on the early treatment diabetic retinopathy grid) at Screening Visit 1.
  • CNV lesion characteristics as assessed by the CRC: lesion size needs to be less than 10-disc areas (typical disc area = 2.54 mm^2).
• Must be pseudophakic (at least 12 weeks postcataract surgery) in the study eye.
• Must be willing and able to comply with all study procedures and be available for the duration of the study.
• Women must be postmenopausal (defined as being at least 12 consecutive months without menses) or surgically sterilized (ie, having a bilateral tubal ligation/bilateral salpingectomy, bilateral tubal occlusive procedure, hysterectomy, or bilateral oophorectomy).
• Male participants engaged in a sexual relationship with a woman of childbearing potential must be willing to use condoms (and their partners to use a medically accepted method of contraception) from the day of RGX-314 administration until 4 weeks after RGX-314 administration.
• Must be willing and able to provide written, signed informed consent.
• Response criteria: Based on the Screening Visit 2 SD-OCT, participants must have improvement in fluid of > 50 μm or, if the participant has < 50 μm of fluid, then any improvement in fluid and have a CRT < 400 μm at the screening visit, as determined by the CRC. Note that, if the participant has disease other than fluid contributing to an increase (i.e., pigment epithelial detachment [PED] or subretinal hyper-reflective material [SHRM]) in CRT, they will be enrolled if they have < 50 μm of fluid (intraretinal or subretinal), as determined by the CRC.
• Additionally, participants who received 10 to 12 anti-VEGF injections in the study eye in the 12 months prior to Screening Visit 1 must demonstrate a complete fluid response as determined by CRC review of the Screening Visit 2 SD-OCT, defined as complete resolution of fluid.

• CNV or macular edema in the study eye secondary to any causes other than AMD.
• Subfoveal fibrosis or atrophy as determined by the CRC.
• Study eye that required > 12 anti-VEGF injections in the 12 months prior to the Screening Visit
• Any condition in the investigator’s opinion that could limit VA improvement in the study eye.
• Active or history of retinal detachment in the study eye.
• Advanced glaucoma in the study eye defined as IOP of > 23 mmHg not controlled by 2 IOP-lowering medications or any invasive procedure to treat glaucoma (e.g., shunt, tube, or minimally invasive glaucoma surgery [MIGS] devices; selective laser trabeculectomy, and argon laser trabeculoplasty are permitted).
• Study eye with nAMD diagnosed > 4 years from Screening Visit 1.
• Any condition in the study eye that, in the opinion of the investigator, may increase the risk to the participant, require either medical or surgical intervention during the course of the study to prevent or treat vision loss, or interfere with study procedures or assessments.
• History of intraocular surgery in the study eye within 12 weeks prior to Screening Visit 1. Yttrium aluminum garnet capsulotomy is permitted if performed > 10 weeks prior to the Screening Visit 1.
• History of intravitreal therapy in the study eye, such as intravitreal steroid injection or investigational product, other than anti-VEGF therapy, in the 6 months prior to Screening Visit 1.
• Presence of any implant in the study eye at Screening Visit 1 (excluding intraocular lens or MIGS).
• History of malignancy or hematologic malignancy that may compromise the immune system requiring chemotherapy and/or radiation in the 5 years prior to Screening Visit 1. Localized basal cell carcinoma will be permitted.
• Receipt of any investigational product within the 30 days of enrollment or 5 half-lives of the investigational product, whichever is longer.
• Received gene therapy.
• History of retinal toxicity caused by a therapy that may affect VA, eg, chloroquine or hydroxychloroquine.
• Ocular or periocular infection in the study eye that may interfere with the surgical procedure.
• Myocardial infarction, cerebrovascular accident, or transient ischemic attack within the past 6 months.
• Uncontrolled hypertension (systolic blood pressure [BP] > 180 mmHg, diastolic BP > 100 mmHg) despite maximal medical treatment.
• Any participant with the following laboratory values at Screening Visit 1 will be withdrawn from study:
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 2.5 × upper limit of normal (ULN);
  • Total bilirubin > 1.5 × ULN, unless the participant has a previously known history of Gilbert’s syndrome and a fractionated bilirubin that shows conjugated bilirubin < 35% of total bilirubin;
  • Prothrombin time > 1.5 × ULN, unless the participant is anticoagulated:
    • Participants who are anticoagulated will be monitored by local labs and managed per local practice to hold or bridge anticoagulant therapy for the study procedure; consultation with the Medical Monitor is also required;
  • Hemoglobin < 10 g/dL for male participants and < 9 g/dL for female participants;
  • Platelets < 100 × 10^3/μL;
  • Estimated glomerular filtration rate < 30 mL/min/1.73 m^2.
• Currently taking anticoagulation therapy for which holding anticoagulation therapy for RGX-314 administration is not indicated or considered to be unsafe in the opinion of the treating investigator (i.e., retinal surgeon), as well as the physician prescribing anticoagulation for the participant.
• Any concomitant treatment that, in the opinion of the investigator, may interfere with ocular surgical procedure or healing process.
• Known hypersensitivity to ranibizumab or any of its components.
• Has a serious, chronic, or unstable medical or psychological condition that, in the opinion of the investigator or Sponsor, may compromise the participant’s safety or ability to complete all assessments and follow-up in the study.
• Prior corneal transplant in the study eye.
• Pigmentary glaucoma in the study eye.

Inclusion Criteria for Participants in the Control Arm Who Cross Over to RGX-314 Treatment After Week 54:

• Study eye will be the eye that qualified at randomization.
• Study eye has a CRT < 400 μm of fluid or (in cases where a participant may have nonfluid elevation in the CRT, eg, pigment epithelial defect) < 50 μm of excess fluid, as confirmed by the masked CRC.
• Male participants engaged in a sexual relationship with a woman of childbearing potential must be willing to use condoms (and their partners to use a medically accepted method of contraception) from the day of RGX-314 administration until 4 weeks after RGX-314 administration.

• CNV or macular edema in the study eye secondary to any causes other than AMD.
• New subfoveal fibrosis or atrophy since randomization, as determined by the CRC, or any condition preventing VA improvement in the study eye.
• Ocular or periocular infection in the study eye that may interfere with the surgical procedure.
• Myocardial infarction, cerebrovascular accident, or transient ischemic attacks since randomization.
• Uncontrolled hypertension (systolic BP > 180 mmHg, diastolic BP > 100 mmHg) despite maximal medical treatment.
• Any concomitant treatment that, in the opinion of the investigator, may interfere with ocular surgical procedure or healing process.
• History of malignancy or hematologic malignancy that may compromise the immune system requiring chemotherapy and/or radiation since randomization. Localized basal cell carcinoma will be permitted.
• Currently taking anticoagulation therapy for which holding anticoagulation therapy for RGX-314 administration is not indicated or considered to be unsafe in the opinion of the treating investigator as well as the physician prescribing anticoagulation for the participant.

Eligibility last updated 10/27/21. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria
•Patients:

• Patient age 18 or above.
• Confirmed diagnosis of fibromyalgia (FM).
• Patient must be able to understand and provide informed consent and HIPAA authorization.
• Able to speak and read English.

Exclusion Criteria
•Patients:

• Patients < 18 years of age.
• Inability to provide informed consent or HIPAA authorization.
• Individuals that decline study participation.
• Patients without a confirmed diagnosis of FM.

Inclusion Criteria
•Clinicians:

• Clinicians providing care to eligible patients at the Fibromyalgia Clinic and division of General Internal Medicine (Mayo Clinic Jacksonville and Rochester).

Exclusion Criteria
•Clinicians:

• Individuals that decline study participation.

Eligibility last updated 10/1/21. Questions regarding updates should be directed to the study team contact.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 10/18/23. Questions regarding updates should be directed to the study team contact.

• Signed informed consent must be obtained prior to participation in the study.
• Age ≥ 18 years at the date of signing the informed consent form (ICF).
• Newly diagnosed with AML based on 2016 WHO classification (Arber et al 2016) and not suitable for intensive chemotherapy defined as:
  • age ≥ 75;
  • ECOG performance Status 2 or 3, or any of the following comomorbitities: severe cardiac comorbities (including congestive heart failure, LVEF ≤ 50%, chronic stable Angina) , pulmonary comorbidity (DLCO ≤ 65% or FEVI ≤ 65%);
  • moderate hepatic impairment (with total Bilirubin >1.5 to 3x ULN);
  • renal impairment (eGFR ≥ 30 ml/min/1.73m^2 to 45 30 ml/min/1.73m^2); or
  • any other comorbidity (to be documented in the CRF) that the physician judges to be incompatible with intensive chemotherapy must be reviewed and approved by the Novartis Medical Monitor before study enrollment.
• Not planned for hematopoietic stem-cell transplantation (HSCT).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 , 2 or 3.
• AST and ALT ≤ 3 × upper limit of normal (ULN).
• Total bilirubin ≤ 3.0 × ULN (except in the setting of isolated Gilbert syndrome, in which case higher total bilirubin is allowed provided that conjugated bilirubin is ≤ 3.0 x ULN).
• Estimated Glomerular Filtration Rate (eGFR) ≥ 30 mL/min/1.73 m^2 (estimation based on Modification of Diet in Renal Disease (MDRD) formula, by local laboratory)
• Subject is able to communicate with the investigator, and has the ability to comply with the requirements of the study procedures.
• WBC < 25 x10^9 /L (may be reduced with leukopheresis or hyroxyurea).

• Previous treatment at any time, with any of the following antineoplastic agents, approved or investigational; checkpoint inhibitors, venetoclax and hypomethylating agents (HMAs) such as decitabine or azacitidine. Previous treatment for AML, MDS, myelofibrosis, essential thrombocythemia, or polycythemia vera, with the exception of hydroxyurea, growth factors, and supportive care ruxolitinib.
• Prior exposure to TIM-3 directed therapy.
• Subjects with AML-M3 / APL (Acute promyelocytic leukemia) with PML-RARA and patients with AML secondary to Down's syndrome.
• Subjects with CNS leukemia or neurologic symptoms suggestive of CNS leukemia (unless CNS leukemia has been excluded by a lumbar puncture).
• Subjects with concurrent or prior malignancy, except:
  • subject with history of MDS, myelofibrosis, essential thrombocythemia, or polycythemia vera;
  • subject with history of adequately treated malignancy for which the subject has been disease free (absence of residual disease) for at least 1 year and if no anticancer systemic therapy (namely chemotherapy, radiotherapy or surgery) is ongoing or required during the course of the study. Patients who are receiving adjuvant therapy such as hormonotherapy are eligible.
• History of severe hypersensitivity reactions to any ingredient of study drug(s) (azacitidine, venetoclax or MGB453) or monoclonal antibodies (mAbs) and/or their excipients.
• Any concurrent severe and/or uncontrolled medical condition; e.g., active uncontrolled infection or severe infectious disease requiring parenteral antibacterial, antiviral or antifungal therapy (such as severe pneumonia, meningitis, or septicemia).
• Active autoimmune disease requiring systemic therapy (e.g., corticosteroids).
• Subject has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Starfruit within 3 days prior to the initiation of study treatment (C1D1).
• Current use, or use within 14 days prior to randomization of systemic, steroid therapy (> 10 mg/day prednisone or equivalent) or any immunosuppressive therapy.
• Live vaccine administered within 30 days prior to the first day of study treatment (C1D1).
• Cardiac or cardiac repolarization abnormality, including but not limited to any of the following:
  • History of myocardial infarction (MI), angina pectoris, or coronary artery bypass graft (CABG) within 6 months prior to starting study treatment;
  • QTcF > 470 ms at screening (based on mean of triplicate ECG), long QT syndrome or family history of unexplained cardiac death;
  • Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block);
• HIV infection not controlled by standard therapy and/or with known history of opportunistic infection. For countries where HIV status is mandatory: HIV status will be tested during screening using a local test.
• Active Hepatitis B (HBV) or Hepatitis C (HCV) infection. Subjects whose disease is controlled under antiviral therapy should not be excluded.
• Other co-morbidity that, in the opinion of the investigator, predisposes the subject to high risk of noncompliance with the protocol.
• Sexually active males unless they use a condom during intercourse while taking azacitidine and for 3 months after stopping this drug. They should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid. In addition, male participants must not donate sperm for the time period specified above.
• Subject is pregnant or breastfeeding.
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during study treatment and for 30 days after the last dose of venetoclax, 90 days after the last dose of azacitidine (or as per their respective local labels, whichever is longer) and 150 days after the last dose of MBG453. It is currently unknown whether venetoclax may reduce the effectiveness of hormonal contraceptives, and therefore women using hormonal contraceptives should add a barrier method. Highly effective contraception methods include:
  • Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception;
  • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or bilateral tubal ligation at least 6 weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment;
  • Male sterilization (at least 6 months prior to screening/baseline). For female subjects on the study the vasectomized male partner should be the sole partner;
  • Use of oral (estrogen and progesterone), injected or implanted combined hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS) or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception.
• In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment. Women are considered post-menopausal and not of child bearing potential if they have had over 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate [generally age from 40 to 59 years], history of vasomotor symptoms) in the absence of other medical justification or have had surgical bilateral oophorectomy (with or without hysterectomy) or bilateral tubal ligation at least 6 weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential. If local regulations deviate from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the ICF.

Eligibility last updated 11/4/21. Questions regarding updates should be directed to the study team contact.

• Adult patients, 18 years of age and older.
• Present to one of the participating hospitals.
• Have a chief complaint of one of the target diagnoses.
• Are within a certain geographical area (based on zip codes).
• Have a health insurance plan that covers ACH services.
• Have the capacity to consent or could assent with the consent of a health care proxy who is physically present.

• The patient is not suitable for ACH or inpatient hospital care based on:
  • being a nursing home patient;
  • on or requiring dialysis;
  • positive for COVID-19;
  • having discharge order;
  • requiring intensive care unit (ICU) level of care;
  • history of drug abuse.
• Patients will also need to meet the clinical stability criteria.
• Do not have the capacity to consent or assent with the assistance of a health care proxy.

• Enrolled FAITH! Trial participant.
• Men and women, 18 years of age and older.
• African-American race/ethnicity.
• Active email address.

• Not enrolled in the FAITH! Trial.

Eligibility last updated 10/21/21. Questions regarding updates should be directed to the study team contact.

• Enrolled FAITH! Trial participant.
• Men and women, 18 years of age and older.
• African-American race/ethnicity.
• Active email address.

• Not enrolled in the FAITH! Trial.

Eligibility last updated 10/21/21. Questions regarding updates should be directed to the study team contact.

• ≥ 18 years of age.
• Capacity to consent.
• Patients undergoing a clinically indicated.

• Unable or not willing to consent.
• Pregnant women.
• < 17 years of age.
• External/Internal Electrical Devices – Left ventricular Assist Device, pacemaker dependence, implantable cardioverter defibrillator, transcutaneous electrical nerve stimulation (TENS) unit, or spinal cord stimulator.  (Rational – interference with interpretation).

Eligibility last updated 10/29/21. Questions regarding updates should be directed to the study team contact.

• Diagnosed with Opioid Use Disorder (OUD).
• Willing to participate and follow MAT program rules or enrolled in a residential treatment program.
• Willing to wear an armband device and answer questionnaires.
• Cellphone capable of downloading application (those in residential treatment will download upon discharge from the program).

• Active untreated comorbid mental health symptoms.
• Unable to understand or sign informed consent.
• History of heart disease.
• Women currently pregnant.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 11/6/23. Questions regarding updates should be directed to the study team contact.

• Females, age 18 years or older.
• Diagnosed with epithelial ovarian, fallopian tube, or primary peritoneal cancer based on imaging and physician diagnosis.
• Suspected Stage IIIC or IV disease based on clinician staging and imaging.
• Curative intent treatment with platinum-based chemotherapy.
• Planned surgical intervention at some point during treatment course.
• Ability to read English.
• No diagnosed severe cognitive impairment.
• Ability to provide informed consent.
• Ability to utilize technology to watch online modules for the Resilient Living Program.

• Females under 18 years of age.
• Hemiplegia or paraplegia.
• Current pregnancy.